A randomized trial comparing two arms, C2B8 (a chimeric anti-CD20 antibody) and C2B8 plus interferon-alpha, continues to accrue. Nine patients have been treated with antibody alone. All patients tolerated therapy very well with minimal and easily controllable toxicities. One patient did develop a bacteremia with Listeria monocytogenes. This responded rapidly to antibiotic therapy. A separate patient had a brief and self-limited episode of neutropenia one month after completion of treatment. Two patients with mantle cell lymphoma experienced temporary responses but progressed after two months. Five patients with follicular lymphomas have had responses to treatment (three complete and two partial). One patient with advanced follicular lymphoma had a brief response to combined C2B8 and interferon therapy. Further patients are being enrolled. We are very pleased with the results so far. The resistance to antibody evidenced in our first two mantle cell lymphoma patients appears to correlate with rapid clearance of antibody from the circulation. A biopsy of their recurrent tumor was still CD20 positive but showed little evidence of residual C2B8 bound to the surface of the lymphoma cells. We believe that the antibody can be effective for these patients but may be cleared quickly due to rapid turn-over of the malignant cells in this subclass of lymphomas. This would suggest that higher doses could be beneficial. The overall response rate of 56% (72% excluding the mantle cell cases) is very encouraging.